Bacillus cereus is one of the most common causes of posttraumatic and metastatic bacterial endophthalmitis. Endophthalmitis due to this organism is unusually severe and highly refractory to antibiotic therapy. It is generally believed that the activities of bacterial toxins directly influence the severity and final visual outcome of these infections. There is some correlative evidence to support this, but there have been very few studies to directly address the issue. Little is known about the contributions of specific toxins to endophthalmitis. Our primary aims are to (i) identify and isolate the extracellular B. cereus factors that contribute to the severity of pathogenesis, (ii) determine if inactivation of the activities of specific factors will provide a useful strategy for the treatment of this infection, and (iii) assess the value of intraocular detection of bacterial toxins and enzymes, or host markers of tissue damage, in the rapid diagnosis of endophthalmitis. We have demonstrated that hemolysin BL, the major necrotic toxin of B. cereus, is toxic to retinal tissue in vitro and in vivo. We also showed that other factors contribute 40 to 50% of overall toxicity independently of hemolysin BL. We will isolate the remaining toxins using an in vitro retinal toxicity assay, produce neutralizing antibodies to each, and determine whether their neutralization will improve the outcome of septic B. cereus endophthalmitis in rabbits. We will also determine whether neutralization of virulence factors can alter the course of a B. cereus infection. The usefulness of intravitreal detection of B. cereus factors for rapid diagnosis will be assessed.